University of Texas Health Science Center at Houston

About: University of Texas Health Science Center at Houston is a education organization based out in Houston, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 27309 authors who have published 42520 publications receiving 2151596 citations. The organization is also known as: UTHealth & The UT Health Science Center at Houston.

Inactivating mutations in NPC1L1 and protection from coronary heart disease

Abstract: Ezetimibe lowers plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting the activity of the Niemann-Pick C1-like 1 (NPC1L1) protein. However, whether such inhibition reduces the risk of coronary heart disease is not known. Human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug.We sequenced the exons of NPC1L1 in 7364 patients with coronary heart disease and in 14,728 controls without such disease who were of European, African, or South Asian ancestry. We identified carriers of inactivating mutations (nonsense, splice-site, or frameshift mutations). In addition, we genotyped a specific inactivating mutation (p.Arg406X) in 22,590 patients with coronary heart disease and in 68,412 controls. We tested the association between the presence of an inactivating mutation and both plasma lipid levels and the risk of coronary heart disease.With sequencing, we identified 15 distinct NPC1L1 inactivating mutations; approximately 1 in every 650 persons was a heterozygous carrier for 1 of these mutations. Heterozygous carriers of NPC1L1 inactivating mutations had a mean LDL cholesterol level that was 12 mg per deciliter (0.31 mmol per liter) lower than that in noncarriers (P=0.04). Carrier status was associated with a relative reduction of 53% in the risk of coronary heart disease (odds ratio for carriers, 0.47; 95% confidence interval, 0.25 to 0.87; P=0.008). In total, only 11 of 29,954 patients with coronary heart disease had an inactivating mutation (carrier frequency, 0.04%) in contrast to 71 of 83,140 controls (carrier frequency, 0.09%).Naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. (Funded by the National Institutes of Health and others.).

Serum Glucose Level and Diabetes Predict Tissue Plasminogen Activator–Related Intracerebral Hemorrhage in Acute Ischemic Stroke

Abstract: Background and Purpose—Five pretreatment variables (P 300 mg/dL), predicted symptomatic intracerebral hemorrhage (ICH) in the National Institute of Neurological Disorders and Stroke rtPA trial. We retrospectively studied stroke patients treated 33% middle cerebral artery territory hypodensity]), were reviewed in 138 consecutive patients. Variables were evaluated by logistic regression as predictors of all hemorrhage (including hemorrhagic transformation) and symptomatic hemorrhage on follow-up CT scan. Variables significant at P<0.25 level were included in a multivariate analysis. Diabetes was substituted for glucose in a repeat analysis. Results—Symptomati...

A clinical series of resuscitative endovascular balloon occlusion of the aorta for hemorrhage control and resuscitation

Abstract: : BACKGROUND: A requirement for improved methods of hemorrhage control and resuscitation along with the translation of endovascular specialty skills has resulted in reappraisal of resuscitative endovascular balloon occlusion of the aorta (REBOA) for end-stage shock. The objective of this report was to describe implementation of REBOA in civilian trauma centers. METHODS: Descriptive case series of REBOA (December 2012 to March 2013) used in scenarios of end-stage hemorrhagic shock at the University of Maryland, R. Adams Cowley Shock Trauma Center, Baltimore, Maryland, and Herman Memorial Hospital, The Texas Trauma Institute, Houston, Texas. RESULTS: REBOA was performed by trauma and acute care surgeons for blunt (n 4) and penetrating (n 2) mechanisms. Three cases were REBOA in the descending thoracic aorta (Zone I) and three in the infrarenal aorta (Zone III). Mean (SD) systolic blood pressure at the time of REBOA was 59 (27) mm Hg, and mean (SD) base deficit was 13 (5). Arterial access was accomplished using both direct cutdown (n 3) and percutaneous (n 3) access to the common femoral artery. REBOA resulted in a mean (SD) increase in blood pressure of 55 (20)mmHg, and the mean (SD) aortic occlusion time was 18 (34) minutes. There were no REBOA-related complications, and there was no hemorrhage-related mortality. CONCLUSION: REBOA is a feasible and effective means of proactive aortic control for patients in end-stage shock from blunt and penetrating mechanisms. With available technology, this method of resuscitation can be performed by trauma and acute care surgeons who have benefited from instruction on a limited endovascular skill set. Future work should be aimed at devices that allow easy, fluoroscopy-free access and studies to define patients most likely to benefit from this procedure.

The structural biology of type IV secretion systems

Abstract: Type IV secretion systems (T4SSs) are versatile secretion systems that are found in both Gram-negative and Gram-positive bacteria and secrete a wide range of substrates, from single proteins to protein-protein and protein-DNA complexes. They usually consist of 12 components that are organized into ATP-powered, double-membrane-spanning complexes. The structures of single soluble components or domains have been solved, but an understanding of how these structures come together has only recently begun to emerge. This Review focuses on the structural advances that have been made over the past 10 years and how the corresponding structural insights have helped to elucidate many of the details of the mechanism of type IV secretion.

In Vivo Selection of Highly Metastatic Cells from Surgical Specimens of Different Primary Human Colon Carcinomas Implanted into Nude Mice

Abstract: The purpose of these studies was to select and isolate cells with increased liver-metastasizing potential from heterogeneous primary human colon carcinomas (HCCs). Cells derived from a primary HCC classified as Dukes' stage B2 were directly established in culture or were injected into the subcutis, cecum, or spleen of nude mice. Progressively growing tumors were excised, dissociated, and established in culture. Subsequent to implantation into the cecum or spleen of nude mice, cells from all four lines produced only a few liver tumor foci. HCC cells from the few liver metastases were expanded in culture and then injected into the spleen of nude mice to provide a source for further cycles of selection. With each successive in vivo selection cycle, the metastatic ability of the isolated propagated cells increased. Four cycles of selection yielded cell lines with a very high metastatic efficiency in nude mice. In parallel studies using another primary HCC classified as Dukes' stage D, we isolated cell lines that were highly metastatic in nude mice. Successive selection cycles for growth in the liver increased the metastatic properties of the HCC cells, albeit to a lesser extent than it did those of the Dukes' B2 stage HCC. The ability of the HCC cells to produce liver metastases was not due to simple trapping in the liver. In vivo distribution studies using [125I] iododeoxyuridine-labeled tumor cells revealed that, shortly after injection into the spleen, a comparable number of cells with either low or high metastatic properties arrested in the liver. The differences between the low- and high-degree metastatic cells became apparent by 24 h after injection and, by 72 h, only highly metastatic cells survived in the liver. These results demonstrate that hepatic metastasis by HCC cells is a selective process and that the nude mouse model can be useful for isolating highly metastatic HCC cells and for studying the relevant host organ factors that regulate the pathogenesis of metastasis.